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热凝胶介导的原位恶性肿瘤化疗持续药物递送

Thermogel-mediated sustained drug delivery for in situ malignancy chemotherapy.

作者信息

Zhang Yanbo, Ding Jianxun, Sun Diankui, Sun Hai, Zhuang Xiuli, Chang Fei, Wang Jincheng, Chen Xuesi

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, PR China.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2015 Apr;49:262-268. doi: 10.1016/j.msec.2015.01.026. Epub 2015 Jan 8.

Abstract

In the past few decades, the in situ sustained drug delivery platforms present fascinating potential in sentinel chemotherapy of various solid tumors. In this work, doxorubicin (DOX), a model antitumor drug, was loaded into the thermogel of poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide). The moderate mechanical property of DOX-loaded hydrogel was confirmed by rheological test. In vitro degradation revealed the good biodegradability of thermogel. The DOX-loaded hydrogel exhibited the sustained release profiles up to 30days without and even with elastase. The improved in vivo tumor inhibition and reduced side-effects were observed in the DOX-incorporated hydrogel group compared with those in free DOX group. The excellent in vivo results were further confirmed by the histopathological evaluation or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The thermogel with great prospect may be used as an ideal controlled drug delivery platform for the designated and long-term antitumor chemotherapy.

摘要

在过去几十年中,原位持续给药平台在各种实体瘤的前哨化疗中展现出了迷人的潜力。在这项工作中,将模型抗肿瘤药物阿霉素(DOX)负载到聚(丙交酯-共-乙交酯)-嵌段-聚(乙二醇)-嵌段-聚(丙交酯-共-乙交酯)的热凝胶中。通过流变学测试证实了负载DOX水凝胶具有适度的机械性能。体外降解显示热凝胶具有良好的生物降解性。负载DOX的水凝胶在无弹性蛋白酶甚至有弹性蛋白酶的情况下均表现出长达30天的持续释放曲线。与游离DOX组相比,在负载DOX的水凝胶组中观察到体内肿瘤抑制作用增强且副作用减少。组织病理学评估或末端脱氧核苷酸转移酶介导的dUTP缺口末端标记试验进一步证实了出色的体内结果。具有广阔前景的热凝胶可作为用于指定和长期抗肿瘤化疗的理想控释给药平台。

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